The endovascular treatment using a drug-coated balloon (DCB) reduces restenosis and target vessel re-vascularization rate in patients with peripheral artery disease such as claudication and chronic limb-threatening ischemia (CLTI). However, its safety and efficacy in patients with post-below-knee amputation remain unknown. We had a patient with CLTI and a history of below-knee amputation, who suffered a no-flow phenomenon following DCB angioplasty that required above-knee amputation. DCB angioplasty might not be appropriate for those with severe CLTI and histories of amputation.
The present report describes the risk of endovascular treatment using a drug-coated balloon for chronic limb-threatening ischemia patients with a below-knee amputated limb.
As an incremental number of hemodialysis patients, the number of patients who suffer chronic limb-threatening ischemia (CLTI) needing below-knee (BK) amputation has also been increasing and receiving great concern. These patients sometimes have recurrent CLTI due to impaired blood flow. In such case, revascularization for superficial femoral artery (SFA) or above-knee (AK) amputation is required.
In recent years, the safety and efficacy of drug-coated balloon (DCB) have been reported not only for patients with claudication but also with CLTI [
- Tepe G.
- Laird J.
- Schneider P.
- Brodmann M.
- Krishnan P.
- Micari A.
- Metzger C.
- Scheinert D.
- Zeller T.
- Cohen D.J.
- Snead D.B.
- Alexander B.
- Landini M.
- Jaff M.R.
- Trial Investigators I.N.P.A.C.T.S.F.A.
Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.
Circulation. 2015; 131: 495-502
2]. However, its clinical implication for those with CLTI and histories of BK amputation has not been clarified. This case report presents a rare adverse event: the no-flow phenomenon after using DCB for the BK amputated limb.
- Hata Y.
- Iida O.
- Ito N.
- Soga Y.
- Fukunaga M.
- Kawasaki D.
- Fujihara M.
- Kozuki A.
- Takahara M.
- Mano T.
Roles of angioplasty with drug-coated balloon for chronic ischemia in wound healing.
J Endovasc Ther. 2021; 28: 778-787
A 69-year-old man who was dependent on hemodialysis for 14 years due to end-stage diabetic nephropathy was diagnosed with left-limb CLTI and received BK amputation 6 years previously. The following year, his right limb was also amputated at AK due to worsening CLTI. He began to complain of pain due to worsening CLTI in his left knee and was admitted to our institute to consider further endovascular treatment (EVT).
On admission, his blood pressure was 118/62 mmHg and his pulse rate was 80 bpm. We administered him clopidogrel and aspirin. We performed angiography. We initially infused 3000 IU of unfractionated heparin from the sheath and the activated coagulation time was measured every 30 min and maintained above 250 s.
A left lower limb angiography showed diffuse severe stenosis from SFA to the popliteal artery with severe calcification (black arrows in Fig. 1A ). Six-Fr sheath was ipsilaterally inserted via the left common femoral artery for EVT. The diseased SFA was crossed by the 0.014 in. wire and dilated by the 1.5 mm balloon. Intravascular ultrasound showed diffuse severe calcified stenosis accompanying a calcified nodule with 4.5 mm of distal reference lumen diameter. Additional high-pressure dilatation using a 4.0 mm balloon improved SFA to popliteal artery flow while remaining un-dilated calcified nodule, which was estimated by using intravascular ultrasound examination (black arrows in Fig. 1B, C).
Following the DCB dilatations using Lutonix® 4.0 × 150 mm and Lutonix® 4.0 × 100 mm (C.R. Bard, Murray Hill, NJ, USA), peripheral flow immediately vanished (black closed triangles in Fig. 1D). An intravascular ultrasound confirmed neither flow limiting dissection nor thrombus obstruction. Distal angiography via popliteal artery using micro-catheter showed a pooling of contrast agent at the distal portion. Given all together, we suspected the no-flow phenomenon due to DCB-related distal embolization. Repeated blood aspiration from distal SFA and several intra-arterial administrations of nitroglycerin, nitroprusside, and prostaglandin did not improve peripheral flow, and we eventually terminated the EVT session.
Immediately after EVT, he complained of pain and cyanosis inside of his left thigh (Fig. 2). On post-EVT day 2, serum creatinine kinase began to increase. A follow-up left lower limb angiography showed total occlusion at proximal SFA on post-EVT day 4 (black closed triangles in Fig. 1E). New ulcers developed on post-EVT day 5 (red arrows in Fig. 2). He received AK amputation on post-EVT day 6. Pathological analysis showed fibrinoid necrosis and infiltration of inflammatory cells around the peripheral artery obtained from vastus medialis (Fig. 3).
Various chemical substances including paclitaxel and its base materials are embedded in DCB. Ballooning using DCB sometimes causes distal embolization of these materials, resulting in an inflammatory reaction at distal microvasculature. This phenomenon is known as a “downstream effect” [
- Ibrahim T.
- Dirschinger R.
- Hein R.
- Jaitner J.
Downstream panniculitis secondary to drug-eluting balloon angioplasty.
JACC Cardiovasc Interv. 2016; 9: e177-e179
4]. A downstream effect is in general transient and no studies reported the association between the downstream effect and lower limb amputation.
- Thomas S.D.
- McDonald R.R.
- Varcoe R.L.
Vasculitis resulting from a superficial femoral artery angioplasty with a paclitaxel-eluting balloon.
J Vasc Surg. 2014; 59: 520-523
As observed in our patient (Fig. 3), animal studies demonstrated the association between DCB treatment and fibrinoid necrosis, chronic inflammation, and nuclear change at peripheral arterioles [
]. Our pathological specimens did not reveal any thrombi, cholesterol crystals, or DCB particles, and we were unable to identify the definite cause of this phenomenon. It is inferred that slow flow due to DCB particles and subsequent thrombus might be the main reason. Accumulation and analysis of cases are considered necessary.
- Kolodgie F.D.
- Pacheco E.
- Yahagi K.
- Mori H.
- Ladich E.
- Virmani R.
Comparison of particulate embolization after femoral artery treatment with IN.PACT admiral versus lutonix 035 paclitaxel-coated balloons in healthy swine.
J Vasc Interv Radiol. 2016; 27: 1676-1685
Although severe downstream effects as in our case are rare, a transient slow flow by DCB angioplasty, probably due to a less sick downstream effect, is sometimes encountered. Several risk factors including CLTI, chronic total occlusion, poor run-off, and long DCB use were reported by Shirai and colleagues [
]. Even though our patient had a long lesion without any BK runoff we used the totally long length of DCB, and then his wound worsened due to no-flow. DCB angioplasty is not contraindicated for those with CLTI in Japan [
- Shirai S.
- Hirano K.
- Mori S.
- Makino K.
- Honda Y.
- Tsutumi M.
- Sakamoto Y.
- Kobayashi N.
- Araki M.
- Yamawaki M.
- Ito Y.
Frequency, predictors, and effect of the slow-flow phenomenon after drug-coated balloon angioplasty for femoropopliteal lesions.
Heart Vessels. 2021; 36: 1818-1824
]. On the contrary, an incremental risk of amputation by DCB angioplasty for such a cohort was alerted by Katsanos and colleagues [
- Reijnen M.M.P.J.
- van Wijck I.
- Zeller T.
- Micari A.
- Veroux P.
- Keirse K.
- Lee S.W.
- Li P.
- Voulgaraki D.
- Holewijn S.
Outcomes after drug-coated balloon treatment of femoropopliteal lesions in patients with critical limb ischemia: a post hoc analysis from the IN.PACT global study.
J Endovasc Ther. 2019; 26: 305-315
]. These previous studies do not include those with post-BK amputation like our patient, and these risks are highlighted in such cases, so careful consideration should be given to DCB use, and DCB length should be minimized.
- Katsanos K.
- Spiliopoulos S.
- Kitrou P.
- Krokidis M.
- Paraskevopoulos I.
- Karnabatidis D.
Risk of death and amputation with use of paclitaxel-coated balloons in the infrapopliteal arteries for treatment of critical limb ischemia: a systematic review and meta-analysis of randomized controlled trials.
J Vasc Interv Radiol. 2020; 31: 202-212
The patients with post-BK amputation often have long lesions without any runoff. Given the estimated high risk of severe downstream effects, plain old balloon angioplasty without using DCB might be a safer and more recommended therapeutic strategy for those with post-BK amputation.
Declaration of competing interest
None of the authors has a conflict of interest to disclose in connection with our manuscript.
We acknowledge the pathologist and orthopedic surgeon in our institution for the histopathologic analysis.
- Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.Circulation. 2015; 131: 495-502
- Roles of angioplasty with drug-coated balloon for chronic ischemia in wound healing.J Endovasc Ther. 2021; 28: 778-787
- Downstream panniculitis secondary to drug-eluting balloon angioplasty.JACC Cardiovasc Interv. 2016; 9: e177-e179
- Vasculitis resulting from a superficial femoral artery angioplasty with a paclitaxel-eluting balloon.J Vasc Surg. 2014; 59: 520-523
- Comparison of particulate embolization after femoral artery treatment with IN.PACT admiral versus lutonix 035 paclitaxel-coated balloons in healthy swine.J Vasc Interv Radiol. 2016; 27: 1676-1685
- Frequency, predictors, and effect of the slow-flow phenomenon after drug-coated balloon angioplasty for femoropopliteal lesions.Heart Vessels. 2021; 36: 1818-1824
- Outcomes after drug-coated balloon treatment of femoropopliteal lesions in patients with critical limb ischemia: a post hoc analysis from the IN.PACT global study.J Endovasc Ther. 2019; 26: 305-315
- Risk of death and amputation with use of paclitaxel-coated balloons in the infrapopliteal arteries for treatment of critical limb ischemia: a systematic review and meta-analysis of randomized controlled trials.J Vasc Interv Radiol. 2020; 31: 202-212
Accepted: November 28, 2022
Received in revised form: October 18, 2022
Received: July 6, 2022
© 2022 Japanese College of Cardiology. Published by Elsevier Ltd.
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